Health workers act in an exercise dealing with an outbreak of H7N9 avian flu on June 17 in Hebi, China.

On March 31, 2013, the Chinese health ministry quietly notified the World Heath Organization of three mysterious deaths. After developing coughing and sneezing symptoms, the victims' lungs had filled with fluid, and they died gasping for air. The only thing they had in common was being around live chickens. One victim worked at a poultry market, and the other two recently had shopped at one.

Tests revealed what global health officials had feared for decades: There was a new form of avian influenza. “This strain usually caused mild symptoms like redness of the eyes or low-grade respiratory problems in humans,” said Daniel Jernigan, head of the influenza division of the U.S. Centers for Disease Control and Prevention. “We knew it was different and much more severe when it killed three people.”

More than four years later, the virus has spread across southern China and sickened nearly 1,560 people, nearly 40 percent of whom have died. In May, the CDC ranked the influenza strain H7N9 the highest possible threat for viruses at risk of causing a worldwide pandemic ― just a year shy of the 100th anniversary of the Spanish flu outbreak that claimed nearly 50 million lives in 1918.

Although reports of new infections stopped in March, health officials are worried about the virus changing into a form that’s easily transmitted between humans. A new paper published this summer forecast the virus being three mutations away from such a reality.

“It’s slowly adapting to receptors in humans, and it can spread around the entire globe within a year by people coughing,” said Rick Bright, director of the Biomedical Advanced Research and Development Authority, the government agency in charge of medical countermeasures to national security and public health threats. By contrast, it only took about a year and a half for the 1918 pandemic to kill nearly three times as many people as died in World War I. “That’s when people were traveling on boats. The way we live now with air travel and more people in crowded cities, we could easily have a hot flash,” Bright said.

A new flu outbreak would challenge officials to develop, test, manufacture and distribute millions of doses of an influenza vaccine in time to avert mass casualties. It would also be the biggest test to date of the world’s souped-up surveillance network that has more than doubled in the last couple of decades; there are currently 140 centers in different countries that track and report virus outbreaks.

“We have to monitor this very closely because of all the viruses we have studied so far in the last 20 years, this has the highest potential to mutate to become a pandemic virus,” said Jernigan.

Although warnings of a possible flu pandemic sound terrifying, it’s still a worst-case scenario. Just as it could mutate into something more sinister, it could also become less dangerous. “It could be one of those things that we monitor effectively for the next decade or more, and it never crosses that threshold of efficiently infecting people and causing lots of sickness and death,” said Bright.

So far, the H7N9 strain hasn’t crossed the border from China, and the CDC hasn’t recommended that Americans avoid traveling there (although they should cross live chicken markets off their tour list). And the virus is frustratingly fickle. Case in point: As soon as scientists developed a vaccine for the 2013 strain to be placed into the national stockpile, the virus changed – a phenomenon known as “drift.” Now they’re trying to make another one.

Chasing the vaccine

It currently takes at least six months to produceenough vaccine to cover the U.S. population by culturing the virus in millions of chicken eggs or growing cell lines from dog kidneys. Drug companies are experimenting with other techniques, such as mapping out the virus’ genetic sequence that could shave several months off the entire process – critical days that could help avoid the fiasco of 2009, when the vaccine against the H1N1 swine flu pandemic that killed 17,000 people arrived too late.

“We’ve found ways to improve the yield from batches and figured out ways to make them faster,” said Bright, adding that the U.S. government is partnering with five pharmaceutical companies that collectively have the capacity to produce 600 million doses. (By contrast, nearly 145 million people in the U.S. are vaccinated against the seasonal flu each year.)

Health officials got a wakeup call in 2004 when an influenza strain called H5N1 spread across southeast Asia, and the George W. Bush administration launched a campaign for pandemic flu preparedness that resulted in Congress approving $5.6 billion in part to boost the nation’s drug manufacturing capacity for vaccines and stockpile anti-virals like Tamiflu to treat the sick. “We wanted to ensure our ability to protect everyone in this country and not pick and choose who were the most important,” said Bright. That was on the heels of the SARS pneumonia outbreak in 2003 that resulted in nearly 800 deaths. “We realized that if we had a severe pandemic like in 1918, we wouldn’t be prepared,” added Jernigan.

Holes in the system

Even with vaccines at the ready, the bigger problem might be distributing them using a network of state and county health agencies that are suffering from budget cuts. “How do we administer these to the entire population at once? It’s not like handing out a pill. All this takes money and people and practice, and we just don’t have that right now,” said Jennifer Nuzzo, senior associate for the Johns Hopkins Center for Health Security. “It’s that last mile that will be the hardest.” Hospitals that have lost federal funding for preparedness training might not be equipped to handle an influx of sick patients, either.

Yet the future of influenza prevention might not involve scrambling to reinvent a new vaccine against every threat. “The dream of the moment is to have a universal vaccine with antibodies that will neutralize every known influenza virus that we’ve tested so far,” said Robert Webster, who has studied influenza for 50 years and is emeritus faculty at St. Jude Children’s Research Hospital. Scientists at pharmaceutical giant Johnson & Johnson’s Janssen Vaccines have already started testing one version in mice and ferrets and hope to start the first phase of clinical trials within a year. “We will never eradicate flu, but we’d be in a better place to control it, like measles. You wouldn’t have to get a yearly flu shot,” said Webster.